Rush University Medical Center has just enrolled1 the first U.S. patient in an international clinical trial testing a novel drug to treat certain kinds of melanoma（黑素瘤） , a deadly skin cancer that in its advanced stages currently has few effective treatments. Rather than blocking or killing2 all rapidly dividing cells, whether malignant3（恶性的，有害的） or not, the drug, called nilotnib, is one of a new class of agents that have been designed to sabotage4（妨害，破坏） aberrant5（异常的） molecules6 characteristic of individual cancers – in this case, the c-kit protein.
Dr. Howard Kaufman, director of the Rush University Cancer Center and lead investigator9 of the study at Rush, said that this kind of "targeted" therapy holds out hope of transforming cancer from a lethal10 disease into a chronic11, but manageable disease.
"For advanced melanoma, there are currently few satisfactory treatments," Kaufman said. "But new targeted therapies, including vaccines12, antibodies and small molecules like nilotnib are in clinical trials now, adding to an arsenal13 of treatments that appear to be promising14. This trial is especially significant since the c-kit mutation15 is found more commonly in melanoma arising from the mucosa（粘膜） and foot, which are historically very difficult types of melanoma to treat."
Nilotnib, marketed by Novartis under the brand name Tasigna, is an oral drug approved by the Food and Drug Administration for the treatment of chronic myelogenous leukemia but is now being tested for the first time for the treatment of melanomas that express the c-kit gene16. As a small molecule7, nilotnib is able to slip across the cell's membrane17 and into the machinery18 inside. There it targets, and turns off, the abnormal c-kit protein, created by a mutated c-kit gene, shutting it down and thus disrupting the relay team of molecular19 signals the protein participates in that ultimately spur cell growth and cause melanoma lesions to proliferate20.
Patients with melanomas expressing a mutated c-kit gene are eligible21 to participate in the study. These types of melanomas, which typically occur in mucosal tissue, the eye or the foot, are extremely aggressive. The aim of the trial is to determine whether nilotnib can block the growth and spread of this kind of melanoma and extend life.
Participants will receive either nilotnib or dacarbazine, a chemotherapy drug commonly used to treat advanced melanoma. Those in the latter group will be able to begin receiving nilotnib if their cancer progresses after dacarbzaine treatment.
Melanoma is a rare but deadly disease whose incidence is rising faster than that of any other solid tumor22. According to the National Cancer Institute, there were 68,700 new cases of melanoma in 2009, and more than 8,500 deaths caused by the disease. The cancer typically begins in a mole8（鼹鼠，痣） , but can also lodge23 in other pigmented（有颜色的） tissues, such as in the eye or in the intestines24（肠，内脏） . If caught early, when the disease is superficial, the lesions（损害） can easily be removed surgically25. But if it advances, the prognosis is poor. Median survival is six months to two years.
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